ACC: Device May Prevent Stroke in AF Patients

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Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that the study included only patients who were eligible for warfarin therapy.

ORLANDO, March 28 -- A device to close off the left atrial appendage may be at least as good as warfarin (Coumadin) for stroke and clinical event prevention in atrial fibrillation patients, researchers reported.

The Watchman device was associated with a 32% reduction in the combined rate of stroke, cardiovascular death, and systemic embolic events compared with prolonged warfarin therapy (3.4% versus 5.0%), according to David R. Holmes, M.D., of the Mayo Clinic, and colleagues.

While the Watchman's overall advantage met noninferiority criteria, the 91% reduction in the hemorrhagic stroke rate (0.2% versus 1.9%) met superiority criteria, they reported at the American College of Cardiology meeting here.

However, these benefits in the randomized PROTECT-AF trial came at the price of twofold higher risk for complications (8.7% versus 4.2%), predominantly early pericardial effusion.

Management of atrial fibrillation with a device is potentially a huge advance, noted Ralph G. Brindis, M.D., M.P.H., of the University of California San Francisco and Kaiser Permanente in Oakland, Calif.

Dr. Brindis, vice president of the ACC, was not involved in the study and moderated a press conference where the results were reported.

These patients are at five-fold risk of stroke, which predominantly arises from thrombus accumulation in the left atrial appendage. Warfarin is the cornerstone of prophylaxis but some patients can't tolerate the drug and maintaining the therapeutic range is difficult for many others.

"Issues of anticoagulation are huge for patients," Dr. Brindis said. "Not only is it an inconvenience, but there's a significant bleeding hazard of at least 1% per year."

However, other cardiologists were not enthusiastic about using a device with patients who can tolerate warfarin.

A. John Camm, M.D., of St George's Hospital in London and panelist at the late-breaking clinical trial session, highlighted the risks of device implantation even at a center staffed by operators experienced with transseptal access.

He suggested that the Watchman and similar devices be considered only for moderate- to high-risk patients who cannot tolerate anticoagulation or those who are getting ablation for heart failure.

Co-author Horst Sievert, M.D., of the Cardiovascular Center Frankfurt at Sankt Katharinen in Frankfurt, Germany, agreed that the device would likely be adopted first in patients unable to take warfarin.

"Only later on when we see in practice that this really works, will we take it to those patients who can take warfarin," he declared.

But Dr. Holmes cautioned against discounting patient preference. "If you ask patients in a heart clinic, the one medication they always want to get off is always warfarin."

The Watchman resembles a distal protection device with barbs to keep it in place in the left atrial appendage.

The open-label study included 707 patients with atrial fibrillation and no valvular disease who were eligible for long-term warfarin therapy but had no other conditions that would require it.

Among the participants randomized to receive the device with warfarin for only the first 45 days rather than prolonged warfarin therapy, 90.9% had successful implantation and 86% both got the device in and were able to discontinue warfarin.

These per protocol patients had an even greater reduction in the combined rate of stroke, cardiovascular death, and systemic embolic events compared with warfarin than the intent-to-treat group (relative risk 0.44 and 0.68, respectively).

But Dr. Camm noted that warfarin therapy was not ideal in the trial. INR (international normalized ratio) control was certainly real-life but not ideal or up to the standard expected in an antithrombotic medication study, he said.

For the primary safety endpoint -- the combined rate of device embolization requiring retrieval, pericardial effusion requiring intervention, cranial or gastrointestinal bleeding, and any bleed treated with at least a two-unit transfusion -- was 8.7% with the device, compared with 4.2% in the warfarin group.

The most common of these events was pericardial effusion, which declined over time as operators grew more experienced, the device was made smaller, and operators developed new techniques for implantation.

By the end of the trial, the pericardial effusion rate had dropped from 8.4% to 7.2%. In the post-trial registry, it dropped further to 1.1%.

Stroke was the most serious of the adverse events. Hemorrhagic strokes occurred in six controls compared with one in the device group, which occurred while the patient was still on warfarin at 15 days.

Total mortality was higher among device group patients (17 versus 15), but none of the deaths was deemed procedure- or device-related.

Researchers plan a five-year follow-up, but there's little reason to suspect that the effects won't last, Dr. Holmes said. The left atrial appendage clots off behind the device, which is expected to epithelialize as well.

There were some dislodgements, according to the report. Two occurred in the pilot phase before improvements in design. Another occurred during the main phase of the trial, several months after placement. In that case, the patient was asymptomatic, and doctors discovered the device missing serendipitously during echocardiography. They later retrieved it from the abdomen.

The dislodgement rate may be one in 350 or 400, Dr. Holmes estimated.

The trial was sponsored by Atritech, the company that makes the device.

Dr. Holmes reported that his institution receives research support from Atritech and may receive royalties.

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